Development of metallo-beta-lactamase inhibitors - Dr. Máté Erdélyi

Webinar given by Dr. Máté Erdélyi at the Uppsala Antibiotic Center's seminar series on Friday December 3rd.
Our most common antibiotics are the β-lactam containing ones, such as the penicillins and cephalosporins. In response to their wide use, bacteria have acquired the ability to produce β-lactamases that inactivate β-lactam antibiotics. Metallo-β-lactamases are an especially problematic group of enzymes as these hydrolyze nearly all known β-lactam antibiotics, including carbapenems, which are our last resort drugs. There are very few known metallo-β-lactamase inhibitors, and none of them is clinically applicable. In this talk I will show examples of our research on the development of metallo-β-lactamase inhibitors. These molecules are designed to protect β-lactam antibiotics and thereby allow their extended use in form of combination therapies. I will show examples for the design and synthesis of inhibitors of NDM-1, VIM-2 and CcrA, the evaluation of their bioactivities and the NMR spectroscopic determination of their protein binding site.
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